Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-1 in the Retinal Pigment Epithelium and Interphotoreceptor Matrix: Vectorial Secretion and Regulation

Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play an essential role in both normal and pathological extracellular matrix degradation, and a TIMP has been associated with at least one type of retinal degeneration. We have studied expression of MMP-2 and TIMP-1 by zymography, immunocytochemistry, and immunoblotting in the retinal pigment epithelium (RPE) from normal, aged and diseased retinas. MMPs and TIMPs were found in the rat RPE, interphotoreceptor matrix (IPM), and in media conditioned by human and rat RPE in culture. In other polarized cells, MMPs and TIMP-2 are secreted vectorially towards the basal lamina. In the RPE, however, MMP-2 and TIMP-1 were secreted preferentially from the apical surface, the surface bordering the IPM. These findings provide new evidence that MMPs and TIMPs could play a role in the turnover of IPM components.Cell homogenates and conditioned media from RPE isolated from mutant Royal College of Surgeons (RCS) rats with inherited retinal dystrophy had similar amounts of MMP-2 and TIMP-1 as those from congenic control rats. The secretion of MMP-2 and TIMP-1 from RPE cell cultures isolated from young and aged human donors varied widely. However, with increasing cell passage number, secretion of MMPs and TIMPs from human RPE increased dramatically. Also, growing human RPE on bovine corneal endothelial cell-generated extracellular matrix instead of plastic reduced the secretion of both MMPs and TIMPs. These data suggest that the integrity of Bruch's membrane may serve to regulate RPE functions in MMP and TIMP secretion and that extracellular matrices contain signals that regulate MMP and TIMP synthesis and/or secretion by the RPE.     

Chemical traumatization of adult mouse olfactory epithelium in situ stimulates growth and differentiation of olfactory neurons in vitro

This study demonstrates that ZnSO₄ induced chemical trauma results in an in situ regeneration of the olfactory epithelium which, when maintained in vitro, provides an enriched population of olfactory neurons. Therefore, the ability of the olfactory epithelium to respond to chemical trauma with increased mitotic activity can be used to increase growth of neurons in culture. Tissue obtained from normal or vehicle-treated adult mice produced few olfactory neurons, when maintained in culture, compared to cultures established from tissue following an in situ ZnSO₄ trauma. Maximal neuronal yields were obtained in cultures established from tissue that was removed 4–6 days following chemical trauma. The morphological appearance and the presence of cell specific intermediate filament proteins were used to classify the cell types in these olfactory epithelial cultures. Single cells and aggregates of cells which were immunopositive for keratin, but immunonegative for neurofilament protein and GFAP, were identified as epithelioid. Flattened polygonal cells immunopositive for GFAP were identified as glia. A small population of flattened cells was immunonegative for all of the antibodies used in this study. Cells that had processes were immunonegative for GFAP and keratin. Some were immunopositive for 200 kDa and 160 kDa neurofilament proteins but immunonegative for the 68 kDa neurofilament protein. A few of these cells showed positive immunoreactivity with the olfactory marker protein (OMP) antibody and most likely represented the most mature olfactory neurons in the cultures. This trauma-induced culture model using olfactory tissue from adult mice can serve as a source of CNS neurons for comparison with cultured embryonic neurons.     

重组人表皮生长因子对胬肉切除-羊膜移植后眼表上皮愈合速度的影响

目的观察重组人表皮生因子(rhEGF)对眼表上皮修复的影响及羊膜移植治疗翼状肉的疗效。方法对36例患者40眼的翼状肉施行肉切除－羊膜移植术,术后随机分为(rhEF治疗组(20眼)和药物赋型剂对照组(20眼),分别观察两组角膜上皮愈合速度和结膜上皮覆盖羊膜植片的愈合速度,对全部患者随访3-12个月。结果rhEGF治疗组术后角膜上皮愈合速度[(74983±1998)μm/h]显著高于对照组[(59372±17.197)μm/hP＜0.01];rhEGF治疗组结膜上皮愈合速度[(36.584±7.888)μm/h显著高于对照组[(29．181±5.450) μmh,P＜0.01]。随访全部病例未见复发,结论rhEGF可有效促进眼表上皮的损伤修复,羊膜移植为治疗翼状肉的较好方法。     

The effect of cigarette smoke on the bovine lens

Smoking has recently been identified from epidemiological studies as a possible cause of cataract but the mechanism involved is not known. Therefore, our laboratory has initiated studies aimed at elucidating these mechanisms. Whole bovine lenses were cultured to examine possible effects of cigarette smoke on amino acid uptake and protein synthesis. Cigarette smoke, filtered to remove nicotine and tar which would not reach the eye in vivo, was bubbled through culture medium. Bovine lenses were incubated in this medium in the presence of [¹⁴C]-leucine for four days. A significant decrease in uptake of [¹⁴C]-leucine and a decrease in protein synthesis were found with smoke treated lenses. This is the first demonstration of an effect of cigarette smoke on the lens. Further work is needed to determine how this metabolic upset is mediated and how it could lead to cataract.     

兔眼后房型人工晶体置入后房水内丙二醛测定

应用ＴＢＡ荧光法检测了兔眼单纯晶体囊外摘除后和晶体囊外摘除并后房型人工晶体置入后房水内丙二醛含量，这二种手术后房水内丙二醛含量比正常眼显著增高（Ｐ＜０．００５，Ｐ＜０．００１）。结果提示前房内发生了脂质过氧化反应，这一发现有利于对眼内后房型人工晶体表面细胞反应及前膜形成进一步认识。     

人工晶体植入术后继发青光眼的临床分析

报告14例后房型人工晶体植入术后继发青光眼患者，男性8例，女性6例。均为单眼发病，其中10例发生在术后1个月以内，另4例发生在1～3年以后。其中开角型8例，闭用型6例。7例经抗青光眼药物治疗可控制眼压，4例用激光治疗，另3例需行抗青光眼手术。治疗前矫正视力达0．5以上者为28％，治疗后矫止视力达0．5以上增加至50％。所有病例均眼压控制良好、视力不良原因为青光眼世视神经萎缩，提示早期发现的重要性。     

The Recognition of Hypothalamo-Neurohypophysial Functions by Developing T Cells

Neuropeptide signals and specific neuropeptide receptors have been described in the thymus supporting the concept of a close dialogue between the neuroendocrine and the immune systems at the level of early T-cell differentiation. In this paper, we review recent data about neurohypophysial (NHP)-related peptides detected in the thymus from different species. We suggest that we are dealing in fact with other member(s) of the NHP hormone family, which seems to exert its activity locally through a novel model of cell-to-cell signaling, that of cryptocrine communication. This model involves exchange of signals between thymic epithelial cells and developing thymocytes. The NHP-related peptides have been shown to trigger thymocyte proliferation and could induce immune tolerance of this highly conserved neuroendocrine family.     

Comfort of fenestrated hydrogel lenses

A controlled, double-masked, randomized study was conducted on ten subjects to determine the effect of fenestration size on the initial comfort of hydrogel contact lenses. Four fenestrated lenses were tested, each lens containing four mid-peripheral fenestrations of the same size. The diameter of the fenestrations used in the four lenses ranged from 0.39 to 0.96 mm. An unfenestrated lens was also tested. All lenses were made of HEMA and were ordered with the following specifications: -3.00 D, 14.0 mm diameter, 8.4 mm back central optic radius and 0.06 mm centre thickness. There was a significant negative correlation between comfort and fenestration size, indicating that larger fenestrations are less comfortable. Even the lens with the smallest fenestrations (0.39 mm) was significantly less comfortable than the unfenestrated lens. The implication of this finding is that fenestrations may not be clinically efficacious in view of the poor comfort (and presumably increased mechanical effect of the fenestration edges on the tarsal conjunctiva) of fenestrated lenses.     

Identification of a Membrane Receptor for Retinol-Binding Protein Functioning in the Cellular Uptake of Retinal

Retinol-binding protein (RBP) is the transport protein that carries retinol in the circulation from the liver to its target tissues. The existence of a cell-surface receptor on the target cells, which mediates the uptake of retinol from RBP, has been known since 1975. Recently, it was identified as an integral transmem-brane protein named STRA6 that is inducible by retinoic acid in certain cancer cells. The receptor was found to be highly specific for RBP, with high affinity, and to be localized in all tissues known to require retinol for their function, particularly the pigment epithelium of the eye.